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Current Research and Scholarly Interests

I have clinical research interests in the surgical treatment of epilepsy. I am also interested in new developments in the treatment of craniosynostosis a congenital abnormality of infant's skulls

Clinical Trials

Restore CLINICAL TRIALNot Recruiting

This is a prospective, concurrently controlled, multi-center study to evaluate the safety and
effectiveness of the Spinal Kinetics M6-C artificial cervical disc compared to anterior
cervical discectomy and fusion (ACDF) for the treatment of symptomatic cervical radiculopathy
with or without cord compression. Some participating sites will enroll just M6-C patients,
while others will enroll just ACDF patients.
Patients eligible for study enrollment will present with degenerative cervical radiculopathy
requiring surgical intervention, confirmed clinically and radiographically, at one vertebral
level from C3 to C7.
A total of 243 subjects will be included at up to 20 sites.

Stanford is currently not accepting patients for this trial.For more information, please contact Kara Richardson, 650-736-6171.

Abstract

OBJECTIVE The ability to assess the risk of adverse events based on known patient factors and comorbidities would provide more effective preoperative risk stratification. Present risk assessment in spine surgery is limited. An adverse event prediction tool was developed to predict the risk of complications after spine surgery and tested on a prospective patient cohort. METHODS The spinal Risk Assessment Tool (RAT), a novel instrument for the assessment of risk for patients undergoing spine surgery that was developed based on an administrative claims database, was prospectively applied to 246 patients undergoing 257 spinal procedures over a 3-month period. Prospectively collected data were used to compare the RAT to the Charlson Comorbidity Index (CCI) and the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator. Study end point was occurrence and type of complication after spine surgery. RESULTS The authors identified 69 patients (73 procedures) who experienced a complication over the prospective study period. Cardiac complications were most common (10.2%). Receiver operating characteristic (ROC) curves were calculated to compare complication outcomes using the different assessment tools. Area under the curve (AUC) analysis showed comparable predictive accuracy between the RAT and the ACS NSQIP calculator (0.670 [95% CI 0.60-0.74] in RAT, 0.669 [95% CI 0.60-0.74] in NSQIP). The CCI was not accurate in predicting complication occurrence (0.55 [95% CI 0.48-0.62]). The RAT produced mean probabilities of 34.6% for patients who had a complication and 24% for patients who did not (p = 0.0003). The generated predicted values were stratified into low, medium, and high rates. For the RAT, the predicted complication rate was 10.1% in the low-risk group (observed rate 12.8%), 21.9% in the medium-risk group (observed 31.8%), and 49.7% in the high-risk group (observed 41.2%). The ACS NSQIP calculator consistently produced complication predictions that underestimated complication occurrence: 3.4% in the low-risk group (observed 12.6%), 5.9% in the medium-risk group (observed 34.5%), and 12.5% in the high-risk group (observed 38.8%). The RAT was more accurate than the ACS NSQIP calculator (p = 0.0018). CONCLUSIONS While the RAT and ACS NSQIP calculator were both able to identify patients more likely to experience complications following spine surgery, both have substantial room for improvement. Risk stratification is feasible in spine surgery procedures; currently used measures have low accuracy.

Abstract

We describe a case of a 24-year-old patient with relapsed acute myelogenous leukemia involving the central nervous system. After placement of an Ommaya reservoir for intrathecal chemotherapy administration, the patient developed progressive headache, nausea, and drowsiness and was found to have an enlarging subdural collection underlying the Ommaya. To exclude leakage of the Ommaya system into the subdural space, real-time fluoroscopic and C-arm computed tomographic evaluation of the Ommaya reservoir was performed after iodinated contrast injection into the reservoir. This novel technique demonstrated complete integrity of the Ommaya reservoir without evidence of blockage or leakage of the system. The patient underwent uncomplicated evacuation of the subdural collection without replacement of the Ommaya reservoir and made an excellent recovery. This technique for real-time interrogation of the Ommaya reservoir may have additional utility in the evaluation for Ommaya reservoir dysfunction.

Abstract

Osteochondromas are the most frequent benign bone tumors but only rarely occur along the spinal column and even more rarely induce symptoms from spinal cord compression.We report 2 adult patients, both with a history of hereditary multiple exostoses, who presented with cervical myelopathy secondary to osteochondromas. The first patient is a 22-year-old man with numbness and weakness of his right upper limb and neck pain. Radiologic images showed a bony tumor arising from the C3 lamina with evidence of severe spinal cord compression. The second patient is a 20-year-old woman with weakness of her left upper and lower limbs and progressive numbness of the left hand, as well as neck and back pain. Radiologic images showed a bony tumor arising from the C4 lamina with evidence of significant spinal cord compression and cord signal abnormality. Both patients underwent surgical excision of the epidural mass and pathology confirmed a diagnosis of osteochondroma.We discuss the role of surgical intervention, management, and postoperative follow-up in adult patients with cervical osteochondromas. Recommended management includes radiographic imaging and surgical intervention, particularly when evidence of spinal cord impingement occurs. Consistent postoperative follow-up is necessary to ensure appropriate recovery of neurologic function. Surgical management of cervical osteochondromas typically results in excellent and stable clinical outcomes with rare recurrence.

Abstract

Cervical laminoplasty is an important alternative to laminectomy in decompressing of the cervical spine. Further evidence to assess the utility of laminoplasty is required. We examine outcomes of cervical laminoplasty via a population level analysis in the United States.We performed a population-level analysis using the national MarketScan longitudinal database to analyze outcomes and costs of cervical laminoplasty between 2007 and 2014. Outcomes included postoperative complications, revision rates, and functional outcomes.Using a national administrative database, we identified 2613 patients (65.6% male, mean 58.5 years) who underwent cervical laminoplasty. Mean length of stay was 3.1 ± 2.8 days and mean follow-up was 795.5 ± 670.6 days. The overall complication rate was 22.5% (N = 587), 30-day readmission rate was 7.5% (N = 195), and mortality rate was 0.08% (N = 2, elderly patients only). The complication rate was significantly increased in elderly patients (age >65 years) compared to non-elderly patients (OR 0.751, p

Abstract

Posterior fossa decompression surgeries for Chiari malformations are susceptible to post-operative complications such as pseudomeningocele, external cerebrospinal fluid (CSF) leak, and meningitis. Various dural substitutes have been employed to improve surgical outcomes.This study examined whether the collagen matrix dural substitute type correlated with the incidence of post-operative complications following posterior fossa decompression in adult patients with Chiari I malformations.A retrospective cohort study was conducted on 81 adult patients who underwent an elective decompressive surgery for treatment of symptomatic Chiari I malformations, with duraplasty involving a dural substitute derived from either bovine or porcine collagen matrix. Demographics and treatment characteristics were correlated with surgical outcomes.A total of 81 patients were included in the study. Compared to bovine dural substitute, porcine dural substitute was associated with a significantly higher risk of pseudomeningocele occurrence (OR 5.78, 95% CI 1.65-27.15; P = .01) and a higher overall complication rate (OR 3.70, 95% CI 1.23-12.71; P = .03) by univariate analysis. There was no significant difference in the rate of meningitis, repeat operations, or overall complication rate between the two dural substitutes. In addition, estimated blood loss was a significant risk factor for meningitis (P = .03). Multivariate analyses again demonstrated that porcine dural substitute was associated with pseudomeningocele occurrence, though the association with higher overall complication rate did not reach significance.Dural substitutes generated from porcine collagen, compared to those from bovine collagen, were associated with a higher likelihood of pseudomeningocele development in adult patients undergoing Chiari I malformation decompression and duraplasty.

Abstract

Osteochondromas are the most frequent benign bone tumors but only rarely occur along the spinal column and even more rarely induce symptoms from spinal cord compression.We report 2 adult patients, both with a history of hereditary multiple exostoses, who presented with cervical myelopathy secondary to osteochondromas. The first patient is a 22-year-old man with numbness and weakness of his right upper limb and neck pain. Radiologic images showed a bony tumor arising from the C3 lamina with evidence of severe spinal cord compression. The second patient is a 20-year-old woman with weakness of her left upper and lower limbs and progressive numbness of the left hand, as well as neck and back pain. Radiologic images showed a bony tumor arising from the C4 lamina with evidence of significant spinal cord compression and cord signal abnormality. Both patients underwent surgical excision of the epidural mass and pathology confirmed a diagnosis of osteochondroma.We discuss the role of surgical intervention, management, and postoperative follow-up in adult patients with cervical osteochondromas. Recommended management includes radiographic imaging and surgical intervention, particularly when evidence of spinal cord impingement occurs. Consistent postoperative follow-up is necessary to ensure appropriate recovery of neurologic function. Surgical management of cervical osteochondromas typically results in excellent and stable clinical outcomes with rare recurrence.

Abstract

The functional and molecular similarities and distinctions between human and murine astrocytes are poorly understood. Here, we report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. We found that human astrocytes have abilities similar to those of murine astrocytes in promoting neuronal survival, inducing functional synapse formation, and engulfing synaptosomes. In contrast to existing observations in mice, we found that mature human astrocytes respond robustly to glutamate. Next, we performed RNA sequencing of healthy human astrocytes along with astrocytes from epileptic and tumor foci and compared these to human neurons, oligodendrocytes, microglia, and endothelial cells (available at http://www.brainrnaseq.org). With these profiles, we identified novel human-specific astrocyte genes and discovered a transcriptome-wide transformation between astrocyte precursor cells and mature post-mitotic astrocytes. These data represent some of the first cell-type-specific molecular profiles of the healthy and diseased human brain.

Abstract

Demonstrating the value of spine care requires adequate outcomes assessment. Long-term outcomes are best measured as overall improvement in quality of life (QOL) after surgical intervention. Present registries often require parallel data entry, introducing inefficiencies and limiting compliance. The authors detail the methodology of constructing an integrated electronic health record (EHR) system to collect QOL metrics and demonstrate the effect of data collection on routine clinical workflow. A streamlined approach to collecting QOL data can capture patient data without requiring dual data entry and without increasing clinic visit times.Through extensive literature review, a combination of QOL assessments was selected, consisting of the Patient Health Questionnaire-2 and -9, Oswestry Disability Index, Neck Disability Index, and visual analog scale for pain. These metrics were used to provide assessment of QOL following spine surgery and were incorporated into standard clinic workflow by a multidisciplinary team of surgeons, advanced practice providers, and health care information technology specialists. A clinical dashboard tracking more than 25 patient variables was developed. Clinic flow was assessed and opportunities for improvement reviewed. Duration of clinic visits before and after initiation of QOL measure capture was recorded, with assessment of mean clinic visit times for the 12 months before and the 12 months after implementation.The integrated QOL capture was instituted for 3 spine surgeons in a tertiary care academic center. In the 12-month period prior to initiating collection of QOL data, 806 new patient visits were completed with an average visit time of 127.9 ± 51.5 minutes. In the 12 months after implementation, 1013 new patient visits were recorded, with 791 providing QOL measures with an average visit time of 117.0 ± 45.7 minutes. Initially the primary means of collecting patient outcome data was via paper form, with gradual transition to collection via entry into the electronic medical records system. To improve electronic data capture, paper forms were eliminated and an online portal used as part of the patient rooming process. This improved electronic capture to nearly 98% without decreasing the number of patients enrolled in the process.A systematic approach to collecting spine-related QOL data within an EHR system is feasible and offers distinct advantages over registries that require dual data entry. The process of data collection does not impact patients' clinical visit or providers' clinical workflow. This approach is scalable, and may form the foundation for a decentralized outcomes registry network.

Abstract

Demonstrating the value of spine care requires adequate outcomes assessment. Long-term outcomes are best measured as overall improvement in quality of life (QOL) after surgical intervention. Present registries often require parallel data entry, introducing inefficiencies and limiting compliance. The authors detail the methodology of constructing an integrated electronic health record (EHR) system to collect QOL metrics and demonstrate the effect of data collection on routine clinical workflow. A streamlined approach to collecting QOL data can capture patient data without requiring dual data entry and without increasing clinic visit times.Through extensive literature review, a combination of QOL assessments was selected, consisting of the Patient Health Questionnaire-2 and -9, Oswestry Disability Index, Neck Disability Index, and visual analog scale for pain. These metrics were used to provide assessment of QOL following spine surgery and were incorporated into standard clinic workflow by a multidisciplinary team of surgeons, advanced practice providers, and health care information technology specialists. A clinical dashboard tracking more than 25 patient variables was developed. Clinic flow was assessed and opportunities for improvement reviewed. Duration of clinic visits before and after initiation of QOL measure capture was recorded, with assessment of mean clinic visit times for the 12 months before and the 12 months after implementation.The integrated QOL capture was instituted for 3 spine surgeons in a tertiary care academic center. In the 12-month period prior to initiating collection of QOL data, 806 new patient visits were completed with an average visit time of 127.9 ± 51.5 minutes. In the 12 months after implementation, 1013 new patient visits were recorded, with 791 providing QOL measures with an average visit time of 117.0 ± 45.7 minutes. Initially the primary means of collecting patient outcome data was via paper form, with gradual transition to collection via entry into the electronic medical records system. To improve electronic data capture, paper forms were eliminated and an online portal used as part of the patient rooming process. This improved electronic capture to nearly 98% without decreasing the number of patients enrolled in the process.A systematic approach to collecting spine-related QOL data within an EHR system is feasible and offers distinct advantages over registries that require dual data entry. The process of data collection does not impact patients' clinical visit or providers' clinical workflow. This approach is scalable, and may form the foundation for a decentralized outcomes registry network.

Abstract

The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.

Abstract

OBJECTIVES: Data regarding rehospitalization and emergency department (ED) visits following vagus nerve stimulation (VNS) present data analysis challenges. We present a method that uses California's multiple databases to more completely assay VNS efficacy. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project's California Inpatient and Ambulatory Surgery databases were assayed for all VNS surgeries from 2005 to 2009. Patients were selected by epilepsy diagnosis codes and VNS procedure codes. Patients (total N = 629) were tracked across multiple databases using unique identifiers. Thirty-day and one-year post-implantation rates of VNS complication and healthcare visits were abstracted, along with one-year preoperative hospital and ED use. Statistics included correction for multiple comparisons. RESULTS: The one-year reoperation rate for adult patients (N = 536) was 3.9%; during the second year, an additional 3.2% of patients had reoperations. Within the first 30 days, <2% of patients experienced a complication. Four percent of patients were readmitted to a hospital, and 11.6% of patients visited an ED. The most common reason for rehospitalization or ED visit was seizure. In the first year after VNS, total seizure-related visits (hospitalization and ED) were 17% lower (2.12 visits per year to 1.71; p = 0.03). In the second year following VNS, seizure-related visits were 42% lower (2.21 visits per year to 1.27, p = 0.01). Pediatric patients (N = 93) had comparable results. CONCLUSIONS: VNS surgery has low rates of complications and reoperations and is associated with reduced incidence of seizure-related ED visits and hospital admissions in the first and second postoperative years.

Abstract

BACKGROUND: Spondyloepiphyseal dysplasia (SED) is a rare disease that causes vertebral abnormalities and short-trunk dwarfism. The two forms of SED are congenita and tarda. Each form arises in a genetically distinct fashion and manifests with a different set of complications. SED congenita is more severe, and patients usually display atlantoaxial instability and odontoid hypoplasia. Patients often have various neurologic deficits caused by compression of the spinal cord. The region most affected is the craniovertebral junction (CVJ). METHODS: A review of the PubMed Database, 1970 to the present, was performed using the search term "spondyloepiphyseal dysplasia" and limited to English-language articles. The search identified 22 articles discussing COL2A1 gene mutations and 10 clinical articles describing patients with SED and associated spinal abnormalities. RESULTS: Findings from the literature concerning diagnosis, presenting symptoms, and intervention taken are discussed. Additionally, a patient with a diagnosis of SED congenita who presented with bilateral hand numbness is described. The patient underwent a suboccipital craniotomy; posterior decompression of the foramen magnum, the arch of C1, and the lamina of C2; and instrumented fusion of C1-3 to relieve his symptoms. CONCLUSIONS: In this article, the authors survey the current literature surrounding neurosurgical interventions and present an algorithm for treatment.

Abstract

BACKGROUND: Histoplasmosis is a fungal disease caused by Histoplasma capsulatum, commonly found in the Americas, and Histoplasma duboisii, located in Africa. In the United States, H. capsulatum is prevalent in the Ohio and Mississippi river valleys. In rare circumstances, central nervous system (CNS) histoplasmosis infection can be caused by shunt placement. We present a case report of a 45-year-old woman in whom CNS histoplasmosis developed after having a ventriculoperitoneal (VP) shunt placed for communicating hydrocephalus. A review of the literature on fungal infections after CNS shunt placement as well as treatment options for this subset of patients was undertaken. METHODS: The PubMed database current to 1958 was filtered and limited to English-language articles. Fifty-eight articles were selected for review based on evidence of information regarding the fungal organism responsible for shunt infection, symptoms, treatment, and/or outcomes. Also included in this review is our case study. RESULTS: A thorough analysis of the PubMed database revealed 58 reported cases of CNS shunt-related fungal infections in the English-language medical literature as well as 7 therapeutic agents used to treat patients in whom postshunt fungal infections developed. CONCLUSIONS: We describe the steps in diagnosis of histoplasmosis after shunt placement, provide an effective therapeutic regimen, and review the present understanding of CNS fungal infections. The medical literature was surveyed to compare and analyze various CNS fungal infections that can arise from shunt placement as well as treatments rendered.

Abstract

Giant cell tumors (GCTs) developing from the cranial bones are rare. Occurrence of these tumors in the vicinity of eloquent areas precludes complete excision. Fractionated external beam radiotherapy (FEBRT) has been used for those cases, but with inconsistent outcomes. The authors report a case of a patient with a GCT involving the left occiput which was successfully treated by CyberKnife stereotactic radiosurgery (CK RS). There was improvement in the neurological deficit and occipital pain without adjunctive treatment. This is the first report of stereotactic radiosurgery (SRS) adopted as a primary treatment modality for a cranial GCT.

Abstract

Superficial siderosis (SS) of the central nervous system is a rare condition caused by chronic subarachnoid hemorrhage. Clinical manifestations typically include sensorineural hearing loss and cerebellar ataxia. Recurrent episodic encephalopathy in the setting of SS has not been reported. We describe a unique case of SS in a 67-year-old man with an 8-year history of episodic encephalopathy associated with headache and vomiting. The patient also had a history of progressive dementia, ataxia, and myelopathy. A diagnosis of superficial siderosis was made after magnetic resonance gradient-echo images showed diffuse hemosiderin staining over the cerebellum and cerebral convexities. No intracerebral source of hemorrhage was identified. The patient therefore underwent gadolinium-enhanced spinal MRI which suggested a possible vascular malformation. A therapeutic laminectomy subsequently confirmed an arteriovenous fistula which was resected. In SS, there are often long delays between symptom onset and definitive diagnosis. Early identification is facilitated by magnetic resonance imaging with gradient-echo sequences. When no source of hemorrhage is identified intracranially, then total spinal cord imaging is indicated to assess for an occult source of hemorrhage as occurred in our case.

Abstract

The authors present a novel case of skeletal dysplasia in a 2.8-year-old girl. The patient presented with progressive lower cranial nerve palsy and myelopathy due to constriction at the cervicomedullary junction caused by overgrowth of the occipital bone of the foramen magnum and the C-1. She also had prominent bone overgrowth of the superior orbital ridges, resulting in excessive stretching of periorbital skin and an inability to fully close her eyes.

Abstract

A primary paraspinal leiomyosarcoma invading the spine is an exceedingly rare neoplasm that may clinically mimic a schwannoma. The authors report a case involving a 45-year-old man with a primary leiomyosarcoma of the cervical paraspinal musculature that invaded the spinal canal at C1-2 and subsequently metastasized to the lungs and pancreas. Aggressive treatment consisting of resection of the primary tumor, adjunctive radiation therapy and chemotherapy, and surgical debulking of metastatic disease resulted in local tumor control at the primary site and long-term survival of the patient.

Abstract

To compare endovascular versus surface methods for the induction and reversal of hypothermia during neurosurgery in a multicenter, prospective, randomized study.Patients undergoing elective open craniotomy for repair of an unruptured cerebral aneurysm (n = 153) were randomly assigned (2:1) to undergo whole-body hypothermia to 33 degrees C, either with an endovascular cooling device placed in the inferior vena cava via the femoral vein (n = 92) or with a surface convective air blanket (n = 61). Active rewarming was accomplished using the same devices.Cooling rates in endovascular and surface blanket groups averaged 4.77 and 0.87 degrees C/h, respectively (P < 0.001). When the first temporary arterial or aneurysm clip was placed, 99% of endovascular patients and 20% of surface blanket patients had reached the target of 33 degrees C (P < 0.001). Obese patients were cooled efficiently with the endovascular approach (3.56 degrees C/h). Rewarming rates averaged 1.88 degrees C/h for endovascular patients and 0.69 degrees C/h for surface blanket patients (P < 0.001). By the end of surgery, 89 and 53% of these patients, respectively, had rewarmed to at least 35 degrees C (P < 0.001). On leaving the operating room, 14% of endovascular patients and 28% of surface blanket patients were still intubated (P = 0.035). The overall safety of the two procedures was comparable. No clinically significant catheter-related thrombotic, bleeding, or infectious complications were reported in the endovascular group.Endovascular cooling provided superior induction, maintenance, and reversal of hypothermia compared with the surface blanket, without an increase in complications. Endovascular cooling may have clinical benefit for patients undergoing cerebrovascular surgery, as well as patients with acute stroke, head injury, or acute myocardial infarction.

Abstract

Idiopathic granulomatous inflammation of the pituitary gland occurs rarely, and is usually identified as an incidental finding at autopsy. However, it may present during life as a mass lesion that clinically mimics other more common pituitary gland lesions. We report a 54-year-old woman presenting with acute onset diabetes insipidus whose MRI showed a 1.1 cm pituitary mass, with infundibular thickening and meningeal enhancement. Biopsy demonstrated granulomatous hypophysitis with multinucleate histiocytes. Special studies for infectious organisms were negative. The patient's disease progressed following biopsy, causing complete loss of vision in the right eye. This responded to high-dose steroids and local lowdose radiation. She later developed an acute inferior myocardial infarction. Laboratory tests failed to demonstrate an underlying autoimmune process. While recovering from this myocardial infarction, she succumbed to pulmonary embolism. Autopsy revealed moderate residual chronic infundibular inflammation. No evidence of systemic or residual pituitary granulomatous disease was identified. To the best of our knowledge, this is the first case of idiopathic granulomatous hypophysitis initially diagnosed by biopsy to have post-mortem neuropathologic examination.

Abstract

Coccidiodal meningitis is a devastating complication of disseminated coccidioidomycosis. An animal model of this infection could enhance understanding of the pathogenesis of the disease and lead to improvements in therapy. A rabbit model of central nervous system infection simulating human disease was established using a blind cisternal tap technique to inoculate 4 x 10(3)-1 x 10(6) arthroconidia of Coccidioides immitis into the cisterna magna. Systemic, neurologic, and histopathologic findings of meningitis were observed in all rabbits, but an inoculum of 2 x 10(4) arthroconidia produced a chronic illness in which meningeal endarteritis obliterans was consistently observed. Serial sampling of cerebrospinal fluid demonstrated an inflammatory response. Growth of C. immitis was demonstrated by quantitative fungal culture from brains and proximal spinal cords.

Abstract

The present study was designed to validate our noninvasive ultrasonic technique (pulse phase locked loop: PPLL) for measuring intracranial pressure (ICP) waveforms. The technique is based upon detecting skull movements which are known to occur in conjunction with altered intracranial pressure. In bench model studies, PPLL output was highly correlated with changes in the distance between a transducer and a reflecting target (R2 = 0.977). In cadaver studies, transcranial distance was measured while pulsations of ICP (amplitudes of zero to 10 mmHg) were generated by rhythmic injections of saline. Frequency analyses (fast Fourier transformation) clearly demonstrate the correspondence between the PPLL output and ICP pulse cycles. Although theoretically there is a slight possibility that changes in the PPLL output are caused by changes in the ultrasonic velocity of brain tissue, the decreased amplitudes of the PPLL output as the external compression of the head was increased indicates that the PPLL output represents substantial skull movement associated with altered ICP. In conclusion, the ultrasound device has sufficient sensitivity to detect transcranial pulsations which occur in association with the cardiac cycle. Our technique makes it possible to analyze ICP waveforms noninvasively and will be helpful for understanding intracranial compliance and cerebrovascular circulation.

Abstract

Localization of ictal onset in patients with medically refractory frontal lobe epilepsy is challenging even with intracranial monitoring. We present a series of nine patients with presumed mesial frontal lobe epilepsy in whom successful localization of ictal onset was achieved in most cases. Intracranial electrodes were placed over cingulate and supplementary motor cortex bilaterally, with additional electrodes placed over lateral and inferior frontal lobes as part of an evaluation for epilepsy surgery. Localization of the ictal onset was clearly defined in seven of nine patients and was characterized by a pattern of lower amplitude beta/gamma range frequencies noted in one to four adjacent electrodes arising from cingulate cortex or supplementary motor cortex in six patients. In the remaining patient, ictal onset was characterized by periodic high amplitude spike and slow-wave discharges evolving into a higher voltage faster rhythm. Electrographic onset occurred coincident with or preceded clinical findings. Ictal pattern also did not demonstrate a widespread propagation pattern in most of the recordings in which ictal onset was well localized. Precise localization of ictal onset within the mesial frontal lobe is possible. Rapid propagation to regions within and outside the frontal lobe does not always occur.

Abstract

We report two cases of central neurocytoma; one located in the right lateral ventricle and associated with a distinctly separate primitive neuroectodermal tumor (PNET)/medulloblastoma of the fourth ventricle, and the other admixed with fat cells and arising from the left lateral and third ventricles with extension into the corpus callosum. We discuss that concurrent occurrences of PNET and adipose tissue are not fortuitous events, but an evidence that neurocytomas and PNETs originate in the residual germinal pool from common progenitor cell rests recapitulating features of developing neurons and with a potential for mesenchymal differentiation.

Abstract

Primary neoplasms of the pineal gland are uncommon. Two patients with unusual primary pineal tumors that had similar distinctive histologic features are reported.The surgically resected neoplastic pineal tissue from these patients were examined by light microscopy, immunohistochemistry, and electron microscopy and correlated with the patients' clinical course.These pineal tumors consisted of a mixture of spindle-shaped cells with fibrillated cell processes and many large lipidized and/or granular pleomorphic cells, some of which were multinucleated. These two tumors superficially resembled pleomorphic xanthoastrocytoma and granular cell tumors of the central nervous system. The pleomorphic tumor cells expressed glial fibrillary acidic protein and some also produced retinal S-antigen, a marker for retinal photoreceptor cells. Long-term follow-up (8 years) on one of these patients suggested a relatively "benign" clinical course.It is possible that this newly described tumor may be a distinct subset of pineal gland neoplasias with a favorable biologic behavior despite the histologic features that would suggest otherwise.

Abstract

89 patients with angiographically documented arteriovenous malformations were treated with helium ion Bragg peak radiation. The rate of complete angiographic obliteration 2 years after radiation was 94% in those lesions smaller than 4 cm3 (2.0 cm in diameter), 75% for those 4-25 cm3 and 39% for those larger than 25 cm3 (3.7 cm in diameter); at 3 years after radiation, the corresponding obliteration rates were 100, 95 and 70%. Major clinical complications occurred in 10 patients (8 permanent, 2 transient) between 3 and 21 months after treatment; all were in the initial stage of the protocol (higher radiation doses). 10 patients bled from residual malformation between 4 and 34 months after treatment. Seizures were improved in 63% and headaches in 68% of patients. Excellent or good clinical outcome was achieved in 94% of patients. Compared to the natural history and risks of surgery for these difficult malformations, we consider these results encouraging. Heavy-charged-particle radiation is a valuable therapy for surgically inaccessible symptomatic cerebral arteriovenous malformations. The current procedure has two disadvantages: the prolonged latent period before complete obliteration and the small risk of serious neurological complications.

Abstract

Fetal heart rate was monitored during the administration of esmolol 100 micrograms/kg/min to a 36-year-old, 29-week pregnant woman who was undergoing craniotomy for surgical treatment of six cerebral aneurysms. During stable general anesthesia, sodium nitroprusside was administered to induce moderate hypotension; at the same time, esmolol was infused to control maternal tachycardia. Within minutes after starting the esmolol infusion, maternal heart rate decreased from 100 beats/minute to 65 beats/minute, and fetal heart rate decreased from 160 beats/minute to 130 beats/minute. Upon termination of the infusion 3 hours later, both maternal and fetal heart rate returned to preinfusion values. No adverse effects of esmolol infusion were noted in the mother or fetus.

Abstract

Angiographically occult vascular malformations of the optic nerve and chiasm are extremely rare. Before the advent of magnetic resonance imaging (MRI), it was difficult to diagnose these lesions preoperatively. We report MRI scan findings of optic chiasm cavernous angiomas in two patients with chiasmal syndrome. MRI was useful in localizing the vascular malformation and delineating its characteristics, especially chronic hemorrhage. One patient underwent biopsy of the lesion. The other patient underwent complete microsurgical resection of the malformation with the carbon dioxide laser with preservation of vision. Occult vascular malformations of the optic nerve and chiasm may be a more common cause of visual deterioration than previously recognized. The MRI scan is the imaging modality of choice for diagnosing and following these lesions. In certain patients, these vascular malformations may be amenable to complete surgical removal with stabilization or improvement of visual function.

Abstract

Heavy-charged-particle radiation has several advantages over protons and photons for the treatment of intracranial lesions; it has an improved physical distribution of the dose deep in tissue, a small angle of lateral scattering, and a sharp distal falloff of the dose.We present detailed clinical and radiologic follow-up in 86 patients with symptomatic but surgically inaccessible cerebral arteriovenous malformations that were treated with stereotactic helium-ion Bragg-peak radiation. The doses ranged from 8.8 to 34.6 Gy delivered to volumes of tissue of 0.3 to 70 cm3.Two years after radiation treatment, the rate of complete obliteration of the lesions, as detected angiographically, was 94 percent for lesions smaller than 4 cm3, 75 percent for those of 4 to 25 cm3, and 39 percent for those larger than 25 cm3. After three years, the rates of obliteration were 100, 95, and 70 percent, respectively. Major neurologic complications occurred in 10 patients (12 percent), of whom 8 had permanent deficits. All these complications occurred in the initial stage of the protocol, before the maximal dose of radiation was reduced to 19.2 Gy. In addition, hemorrhage occurred in 10 patients from residual malformations between 4 and 34 months after treatment. Seizures and headaches were less severe in 63 percent of the 35 and 68 percent of the 40 patients, respectively, who had them initially.Given the natural history of these inaccessible lesions and the high risks of surgery, we conclude that heavy-charged-particle radiation is an effective therapy for symptomatic, surgically inaccessible intracranial arteriovenous malformations. The current procedure has two disadvantages: a prolonged latency period before complete obliteration of the vascular lesion and a small risk of serious neurologic complications.

Abstract

In clinical medicine, cerebral ischemia is frequently due to a focal, rather than global, insult. The effect of hyperglycemia in focal cerebral ischemia is not well defined. We studied the effect of hyperglycemia on neuropathologic changes in a rabbit model of focal cerebral ischemia. Rabbits were randomized to receive saline (n = 12) or glucose (n = 12) infusions. The left anterior cerebral and left internal carotid arteries were clipped after the infusion began. After 6 hours of occlusion, the area of severe ischemic neuronal damage in the left neocortex and striatum on two standard sections of brain was calculated and expressed as a percentage of the total area of the left cortex or striatum. The mean +/- SEM cortical area of severe ischemic neuronal damage was 22.1 +/- 2.8% in the glucose-treated rabbits and 34.0 +/- 4.6% in the saline-treated rabbits (p less than 0.05). The cortical area of severe ischemic neuronal damage was inversely correlated with plasma glucose concentration at the time of arterial clipping (p less than 0.05). We conclude that hyperglycemia is associated with decreased histologic neuronal injury in this model of focal cerebral ischemia and may be protective when cerebral ischemia occurs from a focal insult.

Abstract

Hyperglycemia has been reported to worsen the tolerance of the brain to ischemia, and it has therefore been recommended that patients undergoing neurosurgical procedures not receive glucose-containing solutions. However, whereas most animal studies have used global ischemia models, most neurosurgical procedures are associated with risks of focal rather than global ischemia. We therefore studied the effects of glucose administration in an animal model of focal cerebral ischemia. We anesthetized 20 cats with halothane (0.85% end tidal in oxygen), and a focal cerebral ischemic lesion was produced by clip ligation of the left middle cerebral artery using a transorbital approach. Hyperglycemia (10 cats, mean +/- SEM plasma glucose concentration 561 +/- 36 mg/dl) was established before ligation by infusion of 50% glucose in 0.45% saline; the control group (10 cats, mean +/- SEM plasma glucose concentration 209 +/- 28 mg/dl) received 0.45% saline only. Total fluid administered, mean arterial blood pressure, body temperature, and arterial blood gas values did not differ between the two groups 0, 2, and 6 hours after ligation. The cats were killed 6 hours after ligation, and the area of severe ischemic neuronal damage was determined by microscopic examination of a coronal section at the level of the optic chiasm. The mean +/- SEM area of left cortical severe ischemic neuronal damage was 12 +/- 2% of the left cortex in the hyperglycemic group compared with 28 +/- 5% in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

A case of myocardial infarction as a result of coronary vasospasm during percutaneous trigeminal rhizotomy is presented. Potential consequences of the profound sympathetic response during this procedure are discussed. Invasive haemodynamic monitoring as well as prophylaxis with nitrates and calcium antagonists may be useful in patients prone to coronary vasospasm who undergo this procedure.

Abstract

Positive end-expiratory pressure (PEEP) has been used to prevent and treat venous air embolism in patients in the seated position undergoing neurosurgical operations. However, the safety of PEEP has recently been questioned, because of concern that PEEP might increase right atrial pressure (RAP) more than left atrial pressure, thereby predisposing patients with a probe-patent foramen ovale to paradoxical air embolism. In a prior study in dogs, the authors found that to up 10 cm H2O PEEP did not affect the interatrial pressure difference. In the present study, the authors examined the effects of 0, 5, and 10 cm H2O PEEP in 12 anesthetized neurosurgical patients positioned both supine and seated prior to operation. Measurements were made of systemic arterial pressure, RAP, mean pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), and cardiac output. PAWP was higher (average 2 mmHg) than RAP in all patients. PEEP increased RAP and PAWP in patients, both seated and supine (mean 3 mmHg at 10 cm H2O), but did not affect the PAWP-RAP difference. In an additional eight patients in the seated position, the authors examined the effects of 0, 10, and 20 cm H2O PEEP during operation. PEEP again increased PAWP and RAP, but did not significantly affect the PAWP-RAP difference. The PAWP-RAP difference became negative (-1 mmHg) in one patient with 20 cm H2O PEEP. The authors conclude that levels of PEEP up to 10 cm H2O do not alter the interatrial pressure difference in seated neurosurgical patients, and, therefore, would not predispose these patients to paradoxical air embolism.

Abstract

Because of its sensitivity to fluid motion, MR imaging was used to investigate fluid dynamics in syringomyelia. Three major findings characterized syringomyelia: pulsatile fluid in cysts, nonpulsatile fluid in cysts, and damaged cord tissue. The fluid in preoperative syrinx cavities pulsated in a fashion similar to subarachnoid CSF. Pulsation was more prominent in large cysts but was also seen in small cysts. Nonpulsatile cysts were generally of smaller diameter, were shorter in length, and often were single; they could, however, coexist with pulsatile cysts. Nonpulsatile cysts had etiologies similar to those of pulsatile cysts: Chiari malformation, trauma, and unknown. Damaged cord, characterized by abnormal high signal on T2-weighted sequences, was seen in 15 of 16 patients and could be either focal or diffuse but was always adjacent to syrinx cavities. Postsurgical MR scans had a lower incidence of pulsatile cysts. In five patients with both pre- and postoperative MR scans, shunting of the cyst reduced the size of the pulsating cyst (two patients) or reduced the size of the cyst and eliminated pulsation altogether (three patients). Axial, T2-weighted images are recommended in the investigation of spinal cord cysts to determine the presence or absence of pulsatile fluid. The presence of pulsation indicates a nonneoplastic cyst. The absence or reduction of CSF pulsation may prove to be a valuable indicator of the success of a shunting procedure.

Abstract

Malignant astroglial neoplasms of the cerebellum are rare and the clinical behavior of these tumors is unpredictable. The authors describe the histological characteristics and clinical outcome in 10 patients; eight had malignant cerebellar astrocytomas, and one each had an astroblastoma and a true polar spongioblastoma. Malignant glial tumors involving the cerebellum usually behave very aggressively. Cerebellar astroblastomas and polar spongioblastomas are too rare to predict their natural history. Some hypotheses are proposed concerning the evolution and interrelationship of malignant glial tumors of the cerebellum.

Abstract

Intraoperative ultrasound (US) was compared to computed tomography (CT) in 41 intracranial and 6 spinal cord tumors. The studies correlated closely except for primary gliomas. Eight of the 22 primary intracranial gliomas (37%), including 1 low-grade and 7 anaplastic tumors, were larger and more extensive on US than on CT. Margins of non-enhanced primary astrocytomas were shown by US but not CT. Four anaplastic tumors (19%) exhibited echogenicity extending beyond the enhanced area. In 4 patients an enhanced lesion contained a lucent center which proved to be echogenic. Low-grade astrocytomas were relatively homogeneous on US, while anaplastic astrocytomas were more inhomogeneous. Cysts could be found in both types of astrocytomas and were often small and multiple. The echo pattern was not helpful in differentiating metastases from primary tumors, although all of them had sharp margins. Sonography of the central nervous system can provide valuable information about tumor morphology and margins.

Abstract

Plasma concentrations of diazepam and its major active metabolite nordiazepam were measured in 108 neurosurgical patients taking diazepam in doses of 5 to 40 mg/day for periods from one month to 16 years. Diazepam was used for relief of pain or muscle spasm, or anxiety and sleeplessness associated with these two symptoms, and was considered to be beneficial by 83% of the patients, although use of other drugs confounded this evaluation. Concentrations of total diazepam-nordiazepam ranged from 0 to 2,584 ng/mL, with nordiazepam being the predominant metabolite. "Low" concentrations (less than 250 ng/mL) were found in 35 of the 108 patients, with 19 having concentrations lower than 100 ng/mL. "High" concentrations (greater than 900 ng/mL) were found in 20 patients and did not occur more frequently than in other studies of long-term diazepam ingestion. Even with long-term use, diazepam seemed to retain its efficacy and did not lead to any clear-cut abuse.